1. 1. Addison’s Disease 2. Hypernatremia
By Dr. Zahoor

2. Addison’s Disease What is Addison’s Disease?
It is primary Hypoadrenalism.
Therefore, we will study adrenal gland structure and function first, then we will discuss Addison’s disease.

3. Adrenal Gland Adrenal Gland Anatomy and Function
The human adrenal glands weigh 8-10 gram together. Each adrenal gland is situated above the kidney.
Adrenal gland has outer cortex and inner medulla.
The cortex has three zones:
1. Zona glomerulosa
2. Zona fasciculata
3. Zona reticularis
Adrenal medulla – synthesizes, stores and secrete catecholamines (epinephrine and Norepinephrine).

4. The Adrenal gland lie above the kidney
The adrenal glands lie above the kidneys.
The Adrenal gland lie above the kidney

5. Adrenal Gland Adrenal Cortex – three zones
Zona glomerulosa – secrete aldosterone, mainly controlled by renin angiotensin aldosterone mechanism
Zona fasciculata
Zona reticularis
Produce Cortisol and Androgen. Under feedback control of Hypothalamic – Pituitary – Adrenal (HPA) axis

6. Adrenal gland and its hormone

7. Adrenal Gland
We are mainly concerned with Cortisol production (Zona fasciculata and Zona reticularis)
Glucocorticoids production by Adrenals is under hypothalamic – pituitary control
Pituitary ACTH is secreted in response to hypothalamic CRH (Corticotrophin-Releasing Hormone)
ACTH stimulates the secretion of Cortisol from adrenal

8. Adrenal Gland (cont)
ACTH contain melanocyte stimulating hormone (MSH) like sequences which cause pigmentation when ACTH level is markedly raised
Cortisol when secreted (or synthetic corticosteroid when given to patient) cause negative feedback on the hypothalamus and pituitary and inhibit ACTH release

9. Control of Hypothalamic Pituitary Axis

10. Addison’s Disease Primary Hypoadrenalism
Pathophysiology
In this condition, there is destruction of entire adrenal cortex, therefore, Glucocorticoids, Mineralocorticoids and sex steroids production are reduced
Note – Please remember in hypothalamic – pituitary disease, Mineralocorticoids secretion remains largely intact as it is predominantly stimulated by angiotensin II (Renin angiotensin aldosterone mechanism)

11. Addison’s Disease
In Addison’s disease, reduced Cortisol level leads to increased CRH and ACTH production
If ACTH increases markedly, it causes hyper pigmentation
Addison’s disease is rare, 3-4 cases per million per year
There is female preponderance

12. Addison’s Disease Causes
It is most often caused by auto immune disease (more than 90% in UK)
Other cause is tuberculosis – most common in 3rd World countries

15. Addison’s Disease
Addison’s disease has association with other auto immune conditions e.g. type I DM, pernicious anemia, thyroditis, Hypoparathyroidism, premature ovarian failure

16. Addison’s Disease Clinical Features Symptoms - Weight loss - Weakness
- Amenorrhoea
- Syncope
- Abdominal pain
Signs
- Pigmentation – specially of new scars, palmer
creases, Buccal pigmentation
- Postural hypotension

17. Addison’s Disease Symptoms and Signs

18. Addison’s Disease
Pigmentation (dull, slaty, grey brown) is predominant sign in over 90% of cases
Postural hypotension due to hypovolemia and Na loss is present in 80-90% of cases. Mineralocorticoids deficiency is a cause of hypotension

19. Addison’s Disease – Buccal pigmentation

20. Addison’s Disease Investigation 1- Single Cortisol measurement
Random Cortisol > 550 nmol/L makes the diagnosis of Addison’s unlikely (Normal Random in adult nmol/L )
Random Cortisol below 100 nmol/L during the day is highly suggestive of Addison’s

21. Addison’s Disease
Investigation (cont) 2. Short synacthen test – short ACTH stimulation test -Draw blood for Cortisol (zero time ) - Give ACTH 250 Microgram (o.25mg) i.m. injection - take blood sample after 30 min for Cortisol RESULT - In Addison disease there is minimal or no response to ACTH - In normal subject plasma Cortisol > 460nmol/L either at baseline or at 30 min

23. Addison’s Disease Investigations (cont)
3. High plasma ACTH with low cortisol confirms primary hypoadrenalism
4. Electrolytes and Urea
Hyponatraemia
Hyperkalemia
High urea
5. Blood Glucose – maybe low with hypoglycemia
6. Adrenal antibodies – are present in auto immune adrenalitis

24. Addison’s Disease
Investigations (cont) 7. Chest and abdominal X-rays – may show evidence of tuberculosis and/or calcified adrenals 8. Plasma Renin activity is high due to low serum aldosterone 9. Hypercalcemia and anemia are seen some times

25. Addison’s Disease Treatment
Acute Hypoadrenalism (Adrenal crisis) needs urgent treatment
Patient might present with hypotension, hyponatremia, hyperkalaemia, hypoglycemia, dehydration, pigmentation often with precipitating factors like infection, trauma or operation
The major deficiencies are salt, steroid and glucose

26. Addison’s Disease Treatment of Adrenal crisis (cont)
1 liter of 0.9% saline over 30 to 60 mins
100mg I/V bolus of hydro cortisone
I/V glucose
Several liters of saline are required within 24 hours and hydrocortisone 100mg im 6 hourly until the patient is clinically stable.

27. Addison’s Disease Treatment (cont)
When patient is clinically stable, Oral replacement medication is started
- Hydrocortisone 20mg 8 hourly reducing to 20-30mg in divided doses over a few days
Long term treatment
Replacement of Glucocorticoids and Mineralocorticoids
Tuberculosis must be treated if present

28. Addison’s Disease Treatment (cont)
Adequacy of Glucocorticoid dose is judged by
- normal Cortisol level
- patient clinically feeling better
Adequacy of fludrocortisones replacement is assessed by
- Serum electrolytes restored to normal
- Blood pressure should not fall more than 10mm systolic after 2 minutes of standing
- Plasma Renin activity restored to normal

29. Addison’s Disease Advise to patient
All patients taking replacement steroids should know
- To increase steroid during intercurrent illness, infection, injury, stress, surgery
- carry a steroid card
- wear a Medic-Alert bracelet which gives details of their condition so that replacement therapy can be given if found unconscious
- keep hydrocortisone ampule at home in case oral therapy is impossible

30. Secondary Hypoadrenalism
Secondary Hypoadrenalism may arise from 1 - Hypothalamic – pituitary disease – inadequate ACTH production 2 - Long term steroid therapy – leading to hypothalamic-pituitary-adrenal suppression IMPORTANT – ACTH level is low in secondary Hypoadrenalism

31. Historical Information
Why we call Addison’s disease ?
Because Thomas Addison, British Physician, in year 1855 described 6 cases of Addison’s at Guy’s Hospital in London.
Cause was tuberculosis in all 6 cases
Now TB is controlled in the west so common cause is auto immune disease there

32. One of the most famous and well known President of USA, John F
One of the most famous and well known President of USA, John F. Kennedy, Jan 1961-NOV 1963, suffered from Addison's disease.

33. Thank you

34. By Dr. Zahoor
Hypernatremia

35. Hypernatremia What is Hypernatremia?
Increased serum sodium level, more than 145mEg/L is called Hypernatremia
Important
– Normal serum sodium is mEq/L

36. Hypernatremia
Hypernatremia is generally not caused by excess of Na+, but usually by related deficit of free water in the body, therefore, Hypernatremia often coincides with dehydration
How water is lost?
Perspiration
In breathing
In the feces and urine

37. Hypernatremia Normal plasma osmolality282- 295mosmol/L
Normal urine osmolality 600mosmol/L
(Range 50 – 1400mosmol/L) as kidney can concentrate urine or dilute urine

38. Hypernatremia
Hypernatremia is always associated with increase plasma osmolality, which is a potent stimulus to thirst
Clinical Features
Symptoms of Hypernatremia are non specific
Nausea, vomiting, fever and confusion may occur
Convulsions occur in severe Hypernatremia

39. Hypernatremia Causes of Hypernatremia Diabetes Insipidus
Administration of hypertonic sodium solutions
Drugs e.g. piperacillin
Nephrogenic Diabetes Insipidus – insensitivity to ADH caused by drugs e.g. Lithium, tetracycline, Democlocycline, amphotericin B
- Acute tubular nacrosis
- Osmotic diuresis e.g. total Parenteral nutrition
- Deficient water intake
- Increase water loss through skin or lungs

41. Hypernatremia Investigations Do urine, plasma osmolality and serum
sodium at the same time.
EXAMPLES
In diabetes insipidus (ADH is decreased , it causes decreased water reabsorption, increased water loss by kidneys ) therefore
- Plasma osmolality is high
- Serum sodium is high
- Urine osmolality is low ( less than plasma , 250mosom/L) and urine volume is increased

42. Hypernatremia Examples (cont ) In DEHYDRATION
Serum sodium is increased, plasma osmolality is high
Urine osmolality is increased, urine volume is decreased

43. Hypernatremia Treatment
In ADH deficiency , replace ADH in the form of Desmopressin (analogue of ADH)
Withdraw Nephrotoxic drugs where possible
In severe Hypernatremia ( sodium > 170mmol/l )- 0.9% saline is given. Correct Hypernatremia over a period of 48 hours as rapid correction may lead to cerebral edema.

44. Hypernatremia Treatment (cont ) In les sever Hypernatremia,
(serum sodium > 150mmol/L ) – treatment is 5% glucose or o.45% saline .

45. THANK YOU

46. Case History – A tired patient with weakness and dizziness
A 25 year old woman is referred to outpatients feeling tired all the time. She has lost weight and feels dizzy on standing. She also describes muscle aches and weakness. On examination, she appears suntanned. She has postural hypotension of 90/50mmHg when lying, but 75/40mmHg on standing. You make a clinical diagnosis of Addison’s disease.

47. Questions:
Laboratory investigation are likely to show which of the following?
a. Hypokalaemia
b. Hyperkalaemia
c. Hypernatremia
d. Polycythaemia
The appropriate diagnostic investigation is?
a. Dexamethasone suppression test
b. 24 hour urinary Cortisol
c. Mantoux test
d. Short synacthen test
What is the appropriate long term treatment?
a. Glucocorticoid and Mineralocorticoids replacement
b. Glucocorticoid replacement
c. Mineralocorticoid replacement
d. None of the above

48. Answer:
Answer to Question 1: b. Hyperkalaemia Answer to Question 2: d. Short synacthen test Answer to Question 3: a. Glucocorticoid and Mineralocorticoids replacement

49. Thank you